利用数据库解析高原红细胞增多症与肺动脉高压基因表达差异的关联性

Analysis on relationship between high altitude polycythemia and gene expression difference of pulmonary hypertension by using database

目的利用数据库解析高原红细胞增多症(HAPC)与肺动脉高压(PH)基因表达差异的关联性。方法在GEO数据库中对两种疾病的人类数据集进行检索,利用DAVID数据库进行基因的富集分析和功能注释,并进行基因本体(GO)分析、京都基因与基因组百科全书(KEGG)分析、基因富集(GSEA)分析。结果对GSE29977数据集标准化后进行富集分析,得到1627个差异基因,校正后符合筛选阈值的基因有396个,其中188个上调基因和208个下调基因。对GSE53408数据集标准化后进行富集分析,得到3455个基因,校正后符合筛选阈值的基因有791个,其中695个上调基因和96个下调基因。对两个数据集共同差异基因进行重叠后获得138个共同差异基因,将差异基因与校正后得到的11个差异基因分别进行GO分析、KEGG分析、GSEA分析。生物学过程差异基因主要富集在:中胚层形态生成、初级胚层形成、原肠胚形成;细胞成分差异基因主要富集在:黏附连接、细胞与细胞连接、蛋白酶体调控颗粒碱基亚复合物、主要组织相容性复合体(MHC)Ⅱ类蛋白复合物、复杂炎性体等;分子功能差异基因主要富集在:激活转录因子、MHCⅡ类受体活性、UDP葡萄糖基转移酶活性、腺苷脱氨酶活性、磷酸酪氨酸残基结合、半胱氨酸型内肽酶活性参与凋亡信号通路、胰岛素样生长因子Ⅰ结合等。该次分析结果与人类PH疾病所有基因重合的基因有60个,与PH高度相关的基因有血管紧张素转换酶、微小RNA、SMAD通路蛋白、纤维母细胞生长因子(FGF)、血小板衍生生长因子。校正后获得的11个差异基因与之重合的有5个相同基因:FGF18、人类白细胞抗原DQB1、AT结合基序锌指蛋白1、基质金属肽酶8、H因子。结论目前关于HAPC与PH分子机制的研究较少,现有数据分析发现HAPC与PH间具有一些高度相关的差异基因,也呈现出各自疾病所具有的一些特殊基因表达,提示进行更多相关研究和功能验证的必要性。

Objective To use the database to analyze the relationship between high altitude polycythemia(HAPC)and gene expression difference of pulmonary hypertension(PH).Methods The human data sets for these two diseases were retrieved in the GEO database.The gene enrichment analysis and functional annotation were performed by using DAVID database,and the the gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and GSEA analysis were performed.Results The enrichment analysis was performed after the GSE29977 data set standardization,1627 differential genes were obtained,there were 396 genes conforming to the threshold value after correction,in which there were 188 up-regulated genes and 208 down-regulated genes.The enrichment analysis was performed after the GSE53408 data set standardization,3455 genes were obtained,there were 791 genes conforming to the screening threshold value after correction,including 695 up-regulated genes and 96 down-regulated genes.A total of 138 common differential genes were obtained by overlapping common differential genes in two data sets.The GO,KEGG and GSEA analyses were performed on the differential genes and the 11 differential genes obtained after correction.The differentially expressed genes in biological processes were mainly enriched in mesoderm morphogenesis,primary germ layer formation and gastrulation.The differentially expressed genes in cell component were mainly enriched in adhesion junction,cell-cell junction,proteasome regulatory granule alkali subunit complex,MHCⅡprotein complex,complex inflammatory body,etc.The genes with differential molecular functions were mainly enriched in activating transcription factor,MHC classⅡreceptor activity,UDP glucosyltransferase activity,adenosine deaminase activity,phosphotyrosine residue binding,cysteine endopeptidase activity participating in apoptosis signaling pathway,insulin-like growth factorⅠbinding,etc.This analysis results showed that 60 genes overlapped with all the genes of human PH diseases,and the genes highly correlated with PH included angiotensin converting enzyme,microRNA,SMAD pathway protein,fibroblast growth factor(FGF)and platelet-derived growth factor.Among the 11 differential genes obtained after correction,five identical genes overlapped with them:FGF18,human leukocyte antigen DQB1,AT-binding motif zinc finger protein 1,matrix metallopeptidase 8 and H factor.Conclusion At present,there are few studies on the molecular mechanism of HAPC and PH.The existing data analysis finds that there are some highly correlated differentially genes between HAPC and PH and also show some specific gene expressions of the respective diseases,suggesting the necessity for conducting more relevant studies and functional verification.